1. Field of the Invention
Acoustic sensors which employ resonators have been used as detection devices for biological molecules for the past two decades, exhibiting sensitivity in the ng/ml range. They share with optical devices an ability to produce evanescent waves that propagate a limited distance across the solid liquid interface, so molecular events and processes in the bulk are not detected; only those processes leading to interfacial elasticity, viscosity, viscoelasticity and slippage are detected.
2. The Prior Art
However there are significant problems with these systems. As the dimensions of the molecules of interest range from 5 to 20 nm, a substantial amount (>95%) of acoustic transverse coupling is to the fluid above the chemical interface, essentially outside of the domain of the analysis in which there is interest.
An evanescent sensing region that is significantly thicker than the chemical layer of interest leads to reduced sensitivity and interpretation complications. For example, optical SPR (surface plasmon resonance) sensors generate a 200 nanometre evanescent wave, that is supposed to measure the refractive index of the protein layer, and yet it is the composite refractive index of the film and more significantly the fluid that is determined. Similarly electroded piezoelectric crystals known as TSMs (thickness shear mode) or QCMs (quartz crystal microbalances) operate at 10 MHz, which also have an evanescent penetration depth that reaches beyond the chemical layer of interest. Focusing the evanescent wave towards the interface has been attempted with magnetic acoustic resonance sensors that work at 50 MHz, however wave penetration still overshoots the interfacial chemistry with losses in sensitivity. Surface acoustic wave devices known as the Love wave device can work at higher frequencies for smaller penetration depths, however none of these systems provide a sufficiently compact evanescent zone to fully recover the biochemical signal.
A further restriction of these sensors is that a very limited window of information is recovered, at a single wavelength or frequency. This is tantamount to operating an IR spectrometer at a single wavelength, which severely reduces the value of the data recovered.
With respect to the practical format of these systems, all optical and acoustic devices require additional layers of metallisation to be applied and patterned, which for the interdigitated pattern on SAW (surface acoustic wave) is an especially costly process. In-use optical sensing systems require careful alignment and isolation from sources of vibration. Whilst the materials used in MARS (magnetic acoustic resonance sensor) and SAW are sensitive to temperature and demand careful environmental control in order to function without signal drifts. Wire connections to QSM and SAW devices are required, which reduces compatibility with chemical immobilisation modifications and procedures and places design constraints on commercial instruments.
The present invention aims to overcome the above limitations of conventional acoustic sensors.